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The parapoxvirus Orf virus ORF116 gene encodes an antagonist of the interferon response

Basheer A AlDaif1, Andrew A Mercer1, Stephen B Fleming1

  • 1Virus Research Unit, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.

The Journal of General Virology
|December 10, 2021
PubMed

Insights

The Orf virus (ORFV) ORF116 gene modulates innate immune responses, specifically interferon-stimulated genes (ISGs) and inflammatory cytokines. This study reveals ORF116

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Orf virus (ORFV) possesses immunomodulatory genes affecting innate immunity during early infection.
  • ORF116 is a novel ORFV gene with an uncharacterized function.
  • Understanding viral gene functions is crucial for deciphering host-pathogen interactions.

Purpose of the Study:

  • To investigate the function of the novel ORFV gene ORF116.
  • To determine ORF116's role in viral replication and host immune response modulation.
  • To identify specific host genes regulated by ORF116 during infection.

Main Methods:

  • Generation and characterization of an ORF116 deletion mutant virus.
  • Replication studies in primary lamb testis cells.
  • Gene expression microarray analysis in HeLa cells infected with wild-type ORFV or ORF116 deletion mutant.
  • Validation of gene expression changes using quantitative real-time PCR (qRT-PCR).

Main Results:

  • ORF116 deletion resulted in reduced viral replication and smaller plaque formation.
  • ORF116 is expressed before viral DNA replication.
  • Microarray analysis revealed differential expression of interferon-stimulated genes (ISGs) and IL-8 in ORF116 knockout infections.
  • Specific ISGs upregulated in the knockout included IFI44, RIG-I, IFIT2, MDA5, OAS1, OASL, DDX60, ISG20, and IFIT1.

Conclusions:

  • The ORFV gene ORF116 plays a role in modulating the host's interferon response.
  • ORF116 influences the expression of inflammatory cytokines like IL-8.
  • This study provides the first functional characterization of the ORFV ORF116 gene.
Keywords:
Orf virusimmune modulationinterferoninterferon-stimulated genespoxvirus

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